Interferons and beyond: Induction of antiretroviral restriction factors

Hotter, Dominik; Kirchhoff, Frank

doi:10.1002/jlb.3mr0717-307r

Cited by 31 publications

(23 citation statements)

References 160 publications

(247 reference statements)

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“…Successful infection relies on the ability of the virus to escape endosomal acidification and lysosomal fusion through diverse mechanisms, delivering its genome to the cytoplasm or nucleus depending on the virus type ( 43 – 45 ). For each step of viral replication, the host cell has evolved mechanisms for recognizing and fighting viral infection, mainly by inducing the expression of antiviral restriction factors in bystander cells through type I IFN signaling ( 46 – 48 ). Platelets have been reported to express surface receptors able to mediate binding and entry of various viruses [reviewed in Ref.…”

Section: Platelet Interaction and Response To Virusmentioning

confidence: 99%

Platelets in Immune Response to Virus and Immunopathology of Viral Infections

2018

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Platelets are essential effector cells in hemostasis. Aside from their role in coagulation, platelets are now recognized as major inflammatory cells with key roles in the innate and adaptive arms of the immune system. Activated platelets have key thromboinflammatory functions linking coagulation to immune responses in various infections, including in response to virus. Recent studies have revealed that platelets exhibit several pattern recognition receptors (PRR) including those from the toll-like receptor, NOD-like receptor, and C-type lectin receptor family and are first-line sentinels in detecting and responding to pathogens in the vasculature. Here, we review the main mechanisms of platelets interaction with viruses, including their ability to sustain viral infection and replication, their expression of specialized PRR, and activation of thromboinflammatory responses against viruses. Finally, we discuss the role of platelet-derived mediators and platelet interaction with vascular and immune cells in protective and pathophysiologic responses to dengue, influenza, and human immunodeficiency virus 1 infections.

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Section: Platelet Interaction and Response To Virusmentioning

confidence: 99%

Platelets in Immune Response to Virus and Immunopathology of Viral Infections

2018

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“…Together the data indicate that pDC efficiently sensed HIV-infected T cells via CD4-depedent mechanism to induce IFN-I, which was impaired by Vpr. (Kane et al, 2016), including APOBEC3, SAMHD1 and Mx2 (Hatziioannou and Bieniasz, 2011;Hotter and Kirchhoff, 2018). The results presented here showing that Vpr impaired IFN-I production in pDCs may partly account for Vpr-mediated enhancement of viral replication in SIVinfected monkeys and in HIV-1 infected humanized mice (Gibbs et al, 1995;Hoch et al, 1995) , (Sato et al, 2013).…”

Section: Discussionmentioning

confidence: 55%

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

Wang

Tsao

et al. 2019

Preprint

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Plasmacytoid dendritic cells (pDCs) are the major source of type I interferons (IFN-I) in rapid response to viral infections, with constitutive expression of interferon regulatory factor 7 (IRF7). HIV-1 expresses several accessory proteins to counteract specific IFN-induced host restriction factors. As one abundant virion-associated protein, HIV-1 Vpr remains enigmatic in enhancing HIV-1 infection via unclear mechanisms. Here we report that Vpr impaired IFN-I induction in pDCs to enhance HIV-1 replication in CD4+ T cells. Blockade of IFN-I signaling abrogated the effect of Vpr on HIV-1 replication. Virion-associated Vpr suppressed IFN-I induction in pDC by TLR7 agonists. Modulation of IFN-I induction by Vpr was genetically dependent on its activity of TET2 degradation. We further demonstrate that Vpr-mediated TET2 degradation reduced expression of IRF7 in pDCs. Finally, degradation of TET2 in pDCs by Vpr reduced the demethylation level of the IRF7 promoter via CXXC5-dependent recruitment. We conclude that HIV-1 Vpr functions to promote HIV-1 replication by suppressing TET2-dependent IRF7 expression and IFN-I induction in pDCs. The Vpr-TET2-IRF7 axis provides a novel therapeutic target to control HIV-1 infection.

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“…RFs are intrinsic antiviral factors, which are sometimes regarded as integral part of the innate immune response or some other times an autonomous third branch of the immune system (Yan and Chen, 2012). Unlike other classical components of innate immunity, they are constitutively expressed within the host cells and are generally IFN inducible, thus allowing an immediate response against viral infection through specific targeting of viral/cellular components (Bieniasz, 2003;Hotter and Kirchhoff, 2018). Interestingly, during HCMV infection a subset of classical IFN-stimulated genes (ISGs) may be also induced or upregulated independently of IFN (Ashley et al, 2019).…”

Section: Restriction Factors Vs Hcmv: a Never Ending Fightmentioning

confidence: 99%

Tuning the Orchestra: HCMV vs. Innate Immunity

et al. 2020

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Understanding how the innate immune system keeps human cytomegalovirus (HCMV) in check has recently become a critical issue in light of the global clinical burden of HCMV infection in newborns and immunodeficient patients. Innate immunity constitutes the first line of host defense against HCMV as it involves a complex array of cooperating effectors -e.g., inflammatory cytokines, type I interferon (IFN-I), natural killer (NK) cells, professional antigen-presenting cells (APCs) and phagocytes -all capable of disrupting HCMV replication. These factors are known to trigger a highly efficient adaptive immune response, where cellular restriction factors (RFs) play a major gatekeeping role. Unlike other innate immunity components, RFs are constitutively expressed in many cell types, ready to act before pathogen exposure. Nonetheless, the existence of a positive regulatory feedback loop between RFs and IFNs is clear evidence of an intimate cooperation between intrinsic and innate immunity. In the course of virushost coevolution, HCMV has, however, learned how to manipulate the functions of multiple cellular players of the host innate immune response to achieve latency and persistence. Thus, HCMV acts like an orchestra conductor able to piece together and rearrange parts of a musical score (i.e., innate immunity) to obtain the best live performance (i.e., viral fitness). It is therefore unquestionable that innovative therapeutic solutions able to prevent HCMV immune evasion in congenitally infected infants and immunocompromised individuals are urgently needed. Here, we provide an up-to-date review of the mechanisms regulating the interplay between HCMV and innate immunity, focusing on the various strategies of immune escape evolved by this virus to gain a fitness advantage.

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Interferons and beyond: Induction of antiretroviral restriction factors

Cited by 31 publications

References 160 publications

Platelets in Immune Response to Virus and Immunopathology of Viral Infections

Platelets in Immune Response to Virus and Immunopathology of Viral Infections

HIV-1 Vpr Degrades TET2 to Suppress IRF7 and Interferon Expression in Plasmacytoid Dendritic Cells

Tuning the Orchestra: HCMV vs. Innate Immunity

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